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Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G...

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Autores principales: Gupta, Shreedhara, Igoillo-Esteve, Mariana, Michels, Paul A. M., Cordeiro, Artur T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196259/
https://www.ncbi.nlm.nih.gov/pubmed/22091394
http://dx.doi.org/10.4061/2011/135701
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author Gupta, Shreedhara
Igoillo-Esteve, Mariana
Michels, Paul A. M.
Cordeiro, Artur T.
author_facet Gupta, Shreedhara
Igoillo-Esteve, Mariana
Michels, Paul A. M.
Cordeiro, Artur T.
author_sort Gupta, Shreedhara
collection PubMed
description In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents.
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spelling pubmed-31962592011-11-16 Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery Gupta, Shreedhara Igoillo-Esteve, Mariana Michels, Paul A. M. Cordeiro, Artur T. Mol Biol Int Review Article In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents. SAGE-Hindawi Access to Research 2011 2011-04-04 /pmc/articles/PMC3196259/ /pubmed/22091394 http://dx.doi.org/10.4061/2011/135701 Text en Copyright © 2011 Shreedhara Gupta et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Gupta, Shreedhara
Igoillo-Esteve, Mariana
Michels, Paul A. M.
Cordeiro, Artur T.
Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery
title Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery
title_full Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery
title_fullStr Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery
title_full_unstemmed Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery
title_short Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery
title_sort glucose-6-phosphate dehydrogenase of trypanosomatids: characterization, target validation, and drug discovery
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196259/
https://www.ncbi.nlm.nih.gov/pubmed/22091394
http://dx.doi.org/10.4061/2011/135701
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